forsythiaside and Brain-Ischemia

To study the protective effect of forsythiaside B (FB) against cerebral oxidative stress injury induced by cerebral ischemia/reperfusion (I/R) in mice and explore the underlying mechanism.. Ninety C57BL/6 mice were randomized into sham-operated group, middle cerebral artery occlusion (MCAO) model group, and low-, medium and highdose (10, 20, and 40 mg/kg, respectively) FB groups. The expression levels of MDA, ROS, PCO, 8-OHdG, SOD, GSTα4, CAT and GPx in the brain tissue of the mice were detected using commercial kits, and those of AMPK, P-AMPK, DAF-16, FOXO3 and P-FOXO3 were detected with Western blotting. Compound C (CC), an AMPK inhibitor, was used to verify the role of the AMPK pathway in mediating the therapeutic effect of FB. In another 36 C57BL/6 mice randomized into 4 sham-operated group, MCAO model group, FB (40 mg/kg) treatment group, FB+CC (10 mg/kg) treatment group, TTC staining was used to examine the volume of cerebral infarcts, and the levels of ROS and SOD in the brain were detected; the changes in the protein expressions of AMPK, P-AMPK, DAF-16, FOXO3 and P-FOXO3 in the brain tissue were detected using Western blotting.. In mice with cerebral IR injury, treatment with FB significantly reduced the levels of ROS, MDA, PCO and 8-OHdG, increased the activities of antioxidant enzymes SOD, GSTα4, CAT and GPx, and enhanced phosphorylation of AMPK and FOXO3 and DAF-16 protein expression in the brain tissue (. FB inhibits oxidative stress injury caused by cerebral I/R in mice possibly by enhancing AMPK phosphorylation, promoting the downstream DAF-16 protein expression and FOXO3 phosphorylation, increasing the expression of antioxidant enzymes, and reducing ROS level in the brain tissue.

Topics: AMP-Activated Protein Kinases; Animals; Antioxidants; Brain Ischemia; Infarction, Middle Cerebral Artery; Mice; Mice, Inbred C57BL; Oxidative Stress; Reactive Oxygen Species; Reperfusion; Reperfusion Injury; Superoxide Dismutase

Ischemic stroke is a common type of stroke with a high mortality and morbidity rate. Preventing and controlling cerebral ischemic injury is particularly important. Forsythiaside A (FA) has been reported to have anti‑inflammatory and antioxidant activities. The aim of the present study was to explore the impact of FA on middle cerebral artery occlusion (MCAO)‑induced cerebral ischemic injury in rats. The results indicated that FA markedly increased the percent survival and decreased the neurological deficit score in rats with cerebral ischemic injury. Furthermore, cell apoptosis was significantly inhibited by FA administration, which was accompanied by decreased caspase‑3 and caspase‑9 expression. A marked increase in the expression levels of nuclear factor‑erythroid 2‑related factor 2 (Nrf2), NAD(P)H quinone dehydrogenase 1 and glutathione‑s‑transferase was detected in FA‑treated rats. In addition, treatment with FA reduced malonaldehyde expression, and enhanced the expression of superoxide dismutase and glutathione. Furthermore, endoplasmic reticulum (ER) stress was vastly alleviated by FA treatment, as evidenced by the increased expression of B‑cell lymphoma 2, apoptosis regulator and the downregulated expression of phosphorylated (phospho)‑protein kinase RNA‑like ER kinase (PERK)/PERK, phospho‑inositol‑requiring enzyme 1 (IRE1α)/IRE1α and CCAAT‑enhancer‑binding proteins homologous protein. Taken together, the present study demonstrated that FA attenuated cerebral ischemic damage via mediation of the activation of Nrf2 and ER stress pathways. These data may provide ideas for novel treatment strategies of cerebral ischemic damage.

Topics: Animals; Apoptosis; Brain Ischemia; Endoplasmic Reticulum Stress; Female; Glycosides; Male; Neuroprotective Agents; NF-E2-Related Factor 2; Oxidative Stress; Rats, Wistar; Signal Transduction